In a large number of hypertensive patients and animals with experimental hypertension, the cause of elevated blood pressure cannot be explained on the basis of existing knowledge of this disease. We have previously reported that in addition to the known vasoactive factors, there are unknown factors which may play an important role in the etiology of hypertensive disease. We, therefore, are performing studies on the isolation and characterization of such factors in hypertensive patients and animals with experimental hypertension. In these studies we use various in vivo and in vitro procedures as well as analytical biochemical methods. Studies are also performed on the development of improved animal models and assay techniques to be used in the investigation of such vasoactive factors which contribute to the etiology of hypertension. Among the various study models used are animals with experimental perinephritis hypertension. Thus far, the data suggests that plasma from animals with chronic perinephritis hypertension contains a humoral factor which augments the vascular sensitivity to angiotensin and norepinephrine. Studies on the isolation and characterization of this vasoactive factor will continue. BIBLIOGRAPHIC REFERENCES: Michelakis, A.M., J. Menzie, H. Yoshida, and R. McAllister. Studies on the effect of the sympathetic nervous system on renin release. In "Recent Advances in Hypertension", edited by P. Milliez and M. Safar, 1976, p 211. Menzie, J., L. Hoffman, and A. M. Michelakis. Immunofluorescent localization of renin in mouse submaxillary gland and kidney. Am. J. Physiol. 1977 (in press).